Art was always a part of Russell's life. Growing up in Missouri, he drew sketches and made clay figures of animals. Russell had an intense interest in the wild west and would spend hours reading about it. Russell would watch explorers and fur traders who frequently came through Missouri. Russell learned to ride horses at Hazel Dell Farm near Jerseyville, Illinois, on a famous Civil War horse named Great Britain. Russell's instructor was Col. William H. Fulkerson, who had married into the Russell family. At the age of sixteen, Russell left school and went to Montana to work on a sheep ranch.[5]

Russell came to Montana in 1880 at the age of 16. After an unsuccessful stint working on a sheep ranch, he found work with a hunter and trapper turned rancher named Jake Hoover, who owned a ranch in the Judith Basin, and from whom Russell learned much about the ways of the west. The two men remained lifelong friends.[6] After a brief visit to his family in 1882, he returned to Montana, where he remained for the rest of his life. He worked as a cowboy for a number of outfits, and documented the harsh winter of 1886-1887 in a number of watercolors.[6] Russell was working on the O-H Ranch in the Judith Basin of Central Montana at the time, when the ranch foreman received a letter from the owner, asking how the cattle herd had weathered the winter. Instead of a letter, the ranch foreman sent a postcard-sized watercolor Russell had painted of gaunt steer being watched by wolves under a gray winter sky. The ranch owner showed the postcard to friends and business acquaintances and eventually displayed it in a shop window in Helena, Montana. After this, work began to come steadily to the artist. Russell's caption on the sketch, Waiting for a Chinook, became the title of the drawing, and Russell later created a more detailed version which is one of his best-known works.

Beginning in 1888, Russell spent a period living with the Blood Indians, a branch of the Blackfeet nation.[7] It is believed that much of his intimate knowledge of Native American culture came from this period.[6] Upon returning to white culture in 1889, he found the Judith Basin filling up with settlers, so he worked in more open places for a couple of years before settling in the area of Great Falls, Montana, in 1892, in an attempt to make a living as a full-time artist.[6]

In 1896, Russell married his wife Nancy. He was 32 and she was 18.[6] In 1897, they moved from the small community of Cascade, Montana to the bustling county seat of Great Falls, where Russell spent the majority of his life from that point on. There, Russell continued with his art, becoming a local celebrity and gaining the acclaim of critics worldwide. As Russell was not skilled in marketing his work, Nancy is generally given credit in making Russell an internationally known artist. She set up many shows for Russell throughout the United States and in London, creating many followers of Russell.

In 1913, Russell painted Wild Horse Hunters which depicts riders capturing wild horses, each band of which is dominated by a stallion. He used as much color as an artist could on his mountain landscapes.[8] Russell the artist arrived on the cultural scene at a time when the wild west was being chronicled and sold back to the public in many forms, ranging from the dime novel to the wild west show and soon evolved into motion picture shorts and features of the silent era, the westerns that have become a movie staple. Russell was fond of these popular art forms and made many friends among the well-off collectors of his works, including actors and film makers such as William S. Hart, Harry Carey, Will Rogers and Douglas Fairbanks. Russell also kept up with other artists of his ilk, including fellow Old West painter Edgar Samuel Paxson, painter Edward "Ed" Borein and Will Crawford the illustrator.

On the day of Russell's funeral in 1926, all the children in Great Falls were released from school to watch the funeral procession. Russell's coffin was displayed in a glass sided coach, pulled by four black horses.[9]

Russell produced about 4000 works of art, including oil and watercolor paintings, drawings and sculptures in wax, clay, plaster and other materials, some of which were also cast in bronze.[10]

In 1960, Charles M. Russell Elementary School was built in Missoula, Montana. In 1965, a high school was built on the north side of the Missouri River in Great Falls, Montana and named Charles M. Russell High School, in honor of Russell. Ian Tyson's 1987 album, Cowboyography, includes a song titled "The Gift" telling the story of Russell. Michael Nesmith, of Monkees fame, recorded a song titled "Laugh Kills Lonesome" which was inspired by, and describes the contents of, a well-known Russell painting of the same name. Native Blackfeet folk singer Jack Gladstone wrote a song dedicated to Russell titled "When the Land Belonged to God." The song describes Russell's painting of the same name.

Russell's Piegans sold in 2005 for $5.6 million, more than double the highest price his work had sold for a few years earlier.[14] At auction in 2008, Russell's oil painting The Hold Up (20 Miles to Deadwood) sold for $5.2 million, and his bronze sculpture Buffalo Hunt (which depicted two Native Americans attacking a running bison) sold for $4.1 million.[14] In July 2009, Russell's 1907 watercolor and gouache The Truce went for $2.03 million to an anonymous phone bidder.[15] Russell's 1911 18 inches (460 mm) by 13 inches (330 mm) bronze sculpture, Bronc Twister, auctioned in 2008 for $805,000—far above the $300,000 pre-auction estimate.[16]

In July 2011, the price of Russell's work soared again. His 1892 oil painting Water for Camp (depicting Native American women dipping pots into a stream) and his 1924 watercolor A Dangerous Sport (in which two cowboys lasso a mountain lion) sold for nearly $1.5 million each.[14]

A collection of 30 pieces of Russell's art were sold for several million dollars at the Coeur d’Alene Art Auction (held in Reno, Nevada) in July 2014, setting new records for many pieces. Russell's Trail of the Iron Horse watercolor (depicting a group of horseback Native Americans contemplating railroad track) sold for $1.9 million, while Dakota Chief (which depicts a young Lakota chieftain on horseback) was auctioned for $1.1 million (almost double the last price it commanded). Even small pencil sketches sold for $25,000.[17]

Russell's works comprised a wide variety of topics, including major historical events and everyday life in the west. His work was noted for the frequency with which he portrayed well-known events from the point of view of Native American people instead of the non-Native viewpoint. He was noted for a keen eye on the social undercurrents of society and the meticulous authenticity with which he portrayed the clothing and equipment of both cowboys and Native people.

His portrayal of women has drawn critiques and assessment from historians studying women in the west. The contrasting levels of sensuality in his depictions of white and native women is noted in his artistic transference of sexuality from white to Native women, so as to conform to the moral standards and perceptions of women in his time. Most of Russell's portrayals of white women are shown as "pure" and non-sexual, other than those paintings specifically depicting prostitutes. In contrast, his series of five Keeoma paintings and related images show a sensual native woman, with accompanying legends that Keeoma was a real person that Russell had loved. However, photographs show that the body model for these images was actually Russell's wife, Nancy, who in doing so, critics note, was able to express her sexuality in a way generally not allowed "decent" white women of the time.[18]

Timothy Egan, in his book Lasso the Wind,[19] quotes Russell as saying, "In my book a pioneer is a man who turned all the grass upside down, strung bob-wire over the dust that was left, poisoned the water, cut down the trees, killed the Indian who owned the land and called it progress."

A Quiet Day in Utica also known as Tinning a Dog (1907). Depicts Russell and other actual residents of Utica, Montana, including general store owner Charles Lehman, and ex-slave Mollie Ringwold, hotel owner, saloon-keeper and later cook for the nearby Yogo sapphire mine

Waiting for a Chinook, also known as Last of the 5000. One of several depictions of the winter of 1886–87

Russell, Charles M. Good Medicine: Memories of the Real West Garden City Publishing Company, Garden City, NY, 1930. Includes introduction by Will Rogers and biographical note and dedication by Nancy C. Russell.

Stauffer, Joan, Behind Every Man : The Story of Nancy Cooper Russell, University of Oklahoma Press, Norman, Oklahoma. 2008.